title: 2mit, an intronic gene of Drosophila melanogaster timeless2, is involved in behavioral plasticity.
abstract: BACKGROUND
  Intronic genes represent ~6% of the total gene complement in Drosophila melanogaster and ~85% of them encode for proteins. We recently characterized the D. melanogaster timeless2 (tim2) gene, showing its active involvement in chromosomal stability and light synchronization of the adult circadian clock. The protein coding gene named 2mit maps on the 11(th) tim2 intron in the opposite transcriptional orientation.
  
  
  RESULTS
  Here we report the molecular and functional characterization of 2mit. The 2mit gene is expressed throughout Drosophila development, localizing mainly in the nervous system during embryogenesis and mostly in the mushroom bodies and ellipsoid body of the central complex in the adult brain. In silico analyses revealed that 2mit encodes a putative leucine-Rich Repeat transmembrane receptor with intrinsically disordered regions, harboring several fully conserved functional interaction motifs in the cytosolic side. Using insertional mutations, tissue-specific over-expression, and down-regulation approaches, it was found that 2mit is implicated in adult short-term memory, assessed by a courtship conditioning assay. In D. melanogaster, tim2 and 2mit do not seem to be functionally related. Bioinformatic analyses identified 2MIT orthologs in 21 Drosophilidae, 4 Lepidoptera and in Apis mellifera. In addition, the tim2-2mit host-nested gene organization was shown to be present in A. mellifera and maintained among Drosophila species. Within the Drosophilidae 2mit-hosting tim2 intron, in silico approaches detected a neuronal specific transcriptional binding site which might have contributed to preserve the specific host-nested gene association across Drosophila species.
  
  
  CONCLUSIONS
  Taken together, these results indicate that 2mit, a gene mainly expressed in the nervous system, has a role in the behavioral plasticity of the adult Drosophila. The presence of a putative 2mit regulatory enhancer within the 2mit-hosting tim2 intron could be considered an evolutionary constraint potentially involved in maintaining the tim2-2mit host-nested chromosomal architecture during the evolution of Drosophila species.
authors.affiliation: Dipartimento di Biologia, Università degli Studi di Padova Padova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Baggio
authors.forename: Andrea
authors.initials: A
authors.lastname: Bozzato
authors.forename: Clara
authors.initials: C
authors.lastname: Benna
authors.forename: Emanuela
authors.initials: E
authors.lastname: Leonardi
authors.forename: Ottavia
authors.initials: O
authors.lastname: Romoli
authors.forename: Moira
authors.initials: M
authors.lastname: Cognolato
authors.forename: Silvio C E
authors.initials: SC
authors.lastname: Tosatto
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Costa
authors.forename: Federica
authors.initials: F
authors.lastname: Sandrelli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D016000:Cluster Analysis; D019295:Computational Biology; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics*; D019143:Evolution, Molecular; D040461:Gene Components; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007438:Introns / Q000235:genetics*; D008568:Memory / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009420:Nervous System / Q000378:metabolism; D010802:Phylogeny; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012726:Sexual Behavior, Animal / Q000502:physiology*
chemical_list: C000588816:2mit protein, Drosophila; D029721:Drosophila Proteins; D011956:Receptors, Cell Surface; C549776:timeout protein, Drosophila